Respiratory defenses against infection involve a diverse and complex system. Mechanical barriers limit exposure of the respiratory tract to potential pathogenic organisms, whereas the mucociliary apparatus and cough reflexes work to expel any microbes that may bypass the initial defenses. When microorganisms have gained entry to the lower respiratory tract, the alveolar macrophage and recruited phagocytes may eliminate the culprits before active infection can be established. Only after the failure of the innate immune defenses is a specific immune response mounted. Examination of clinical defects in host defense allows one to understand the importance of the multitude of components of the lung's immune defense system.